The broad objectives of this research are to determine environmental correlates of natural foci of the Lyme disease (LD) spirochete, Borrelia burgdorferi sensu stricto (Bb ss) and closely related spirochetes in the Bb sensu lato (sl) complex in highly endemic areas of the Far West; to elucidate and model landscape ecologic and epidemiologic factors that place humans at elevated risk of exposure to Bb ss infection in meso- and macroscales by means of remote sensing and ground-truthing ecologic studies; and to evaluate intrinsic factors that may affect the reservoir competence of vertebrates or the vector competence of ticks for Bb sl. Environmental correlates of natural foci of LD spirochetes will be determined quantitatively by sampling populations of vector ticks and their small vertebrate hosts in relation to Bb sl infection and over 20 biotic and abiotic factors. Two categorical measures will be used to assess risk of exposure to nymphs of the primary vector tick, Ixodes pacificus, in leaf-litter habitats, an indirect measure (entomologic risk index) based on drag-sampling and direct measures of specific human behaviors (e.g., walking, sitting). A combination of field and laboratory methods will be employed to calculate the relative reservoir potential (Rs) of small mammals for Bb sl in deciduous woodlands. The prevalence of infection in free-living or host-fed ticks and their attendant vertebrates with Bb sl and two other emerging tick-borne disease agents (Ehrlichia spp.) Will be determined by tick xenodiagnosis and with standard microbiologic and genetic techniques. Bb sl isolates cultured from vector ticks, reservoir hosts, or skin lesions of patients with early-stage LD infection will be characterized genetically with several methods, and their phylogenetic relatedness to other genospecies of Bb sl will be determined by maximum parsimony analyses. Risk of human exposure to Bb-infected I. pacificus nymphs inhabiting all three climatic zones and seven major vegetational types of northwestern California (Mendocino County) will be modeled using satellite imagery, geographic information systems, and spatial statistical methods in conjunction with ground-verifying ecologic studies an dLD case surveillance data. Borreliacidal assays will be used to evaluate the potential role of complement in vertebrate-host sera (16 spp.) And anti-complement activity in saliva of human-biting vector ticks (2 spp.) As determinants of reservoir-host competence or vector competence for Bb sl or relapsing fever group spirochetes present in the western USA.